The objective of this research is to create a clinical prototype of a new optical biopsy system based on angle-resolved low coherence interferometry (a/LCI). a/LCI is a novel optical technique that uses interferometric detection of elastically scattered light to probe the nuclear morphology of esophageal epithelium. The ability of a/LCI to obtain quantitative measurements of cellular characteristics, such as nuclear size and optical density, without the need for either exogenous stains or fixatives, makes it an excellent candidate to become a screening tool for in vivo detection of pre-cancerous tissue states such as intraepithelial neoplasia. As its name implies, a/LCI detects the angular distribution of scattered light using a low-coherence interferometer. The technique enables selective detection of the optical field scattered from a small region within probed tissue by exploiting the coherence properties of broadband light. The ability to probe sub-surface cellular morphology is especially important for detecting pre- cancerous changes in epithelial tissues, where changes in the basal cell layer, approximately 100 5m beneath the surface are the most important diagnostic of tissue health. The long-range goal of this research is to create a new a/LCI-based biomedical diagnostic product for the purpose of endoscopically identifying and monitoring neoplastic transformations in humans. The research plan will create and test a clinically viable a/LCI system by achieving the following milestones: (1) conducting multi-site human clinical trials to quantitatively assess clinical utility of a/LCI for surveillance and treatment monitoring of esophageal dysplasia, (2) continuing the innovation of the Phase I hardware and probe design to optimize clinical utility of the a/LCI system and (3) developing software for tissue diagnosis based on a/LCI imaging. PUBLIC HEALTH RELEVANCE: The objective of this research is to develop a new instrument for detecting early stage cancer in human epithelial tissues based on a novel optical spectroscopic technique, angle-resolved low coherence interferometry (a/LCI). The proposed a/LCI instrument will serve as a guide to biopsy and treatment monitoring for clinicians, enabling evaluation of tissue health in situ, prior to tissue removal. This technique has the potential to greatly improve upon the current method of random biopsy for screening and surveillance of early stage epithelial cancers.